Effects of different progestogens on human breast tumor cell growth.

ABSTRACT

OBJECTIVE: To examine the effect of progestogens currently used in hormone therapy on growth of human breast tumor cells. METHODS: MCF-7 cells were incubated in 10 nmol/l progestogens, including progesterone (P4), medroxyprogesterone acetate (MPA), norethisterone acetate (NETA), and cyproterone acetate (CPA), with or without 17ß-estradiol (E(2), 1 nmol/l and 10 nmol/l), as well as E(2) alone. Cell proliferation, apoptosis, and the expression of caspase-3 and proliferating cell nuclear antigen (PCNA) were evaluated. RESULTS: The ratios of apoptosis proliferation significantly increased in cultures with progestogens alone, 1 nmol/l E(2) plus progestogens (except P4), and 10 nmol/l E(2) plus NETA. Caspase-3 significantly diminished in cultures with E(2) alone; this was completely reversed when progestogens were added. MPA alone or with 1 nmol/l E(2) and 10 nmol/l E(2) plus NETA significantly increased caspase-3. Using progestogens alone, except P4, significantly decreased PCNA expression. CONCLUSIONS: The results demonstrate that various progestogens have different effects on growth of breast tumor cells, especially with the combined usage of E(2). Progestogen-induced apoptosis may be partly inhibited with the presence of E(2), but less severe with lower E(2) concentrations. Therefore, the choice of progestogens, as well as the doses of E(2) and/or progestogen, may influence breast cancer risk.